Nuclear magnetic resonance imaging (MRI) is an important modality for both clinical and basic-science imaging applications. A recent notable advance in MRI was the introduction of the “hyperpolarized” noble gases helium-3 (3He) and xenon-129 (129Xe) as novel magnetic-resonance contrast agents (See U.S. Pat. Nos. 5,545,396, 5,785,921, 5,785,953 and 6,123,919 to Albert et al.; and Albert M. S., Cates G. D., Driehuys B, et al., “Biological Magnetic Resonance Imaging Using Laser-polarized 129Xe. ” Nature, 1994, 370:199–201, the contents of these patents and this publication are hereby incorporated by reference herein in their entirety). Nuclear polarization levels approaching 100% can be achieved using hyperpolarized noble gases. This dramatic increase in the polarization compared to that typically achieved at thermal equilibrium (at most 10−4) has presented the opportunity for many new MRI applications.
In particular, the strong MR signal from hyperpolarized gases, combined with an appropriate MRI technique, presents the opportunity for imaging of gases with both high spatial and high temporal resolution. One potential application for such a method is the direct, dynamic visualization of gas flow, which would be extremely useful for characterizing a variety of fluid systems. In the medical field, one such system of substantial importance is the lung.
Imaging the Gas-Flow Dynamics of the Lung
Static, high-resolution MR images of the lung air spaces have been demonstrated following the inhalation of hyperpolarized-3He gas (See Middleton H., Black R. D., Saam B., et al., “MR Imaging with Hyperpolarized He-3 gas”, Magn. Reson. Med., 1995, 33:271–275; Black R. D., Middleton H. L., Cates G. D., et al., “In vivo He-3 MR Images of Guinea Pig Lungs.”Radiology, 1996, 199:867–870; Kauczor H. U., Hofmann D., Kreitner K. F., et al., “Normal and Abnormal Pulmonary Ventilation: Visualization at Hyperpolarized He-3 MR Imaging.” Radiology, 1996, 201:564–568; and MacFall J. R., Charles H. C., Black R. D., et al., “Human Lung Air Spaces: Potential for MR Imaging with Hyperpolarized He-3.” Radiology, 1996, 200:553–558). Many initial investigations of the lung using hyperpolarized gases have concentrated on this static spin-density imaging, which is believed to directly reflect lung ventilation. These studies suggest that 3He “ventilation” imaging shows promise for differentiating healthy lungs from those with pathologies such as chronic obstructive pulmonary disease (See Kauczor H. U., Ebert M., Kreitner K. F., et al., “Imaging of the Lungs Using 3He MRI: Preliminary Clinical Experience in 18 Patients with and without Lung Disease”, J. Magn. Reson. Imaging, 1997, 7:538–543; and de Lange E. E., Mugler III J. P., Brookeman J. R., et al., “Lung Air Spaces: MR Imaging Evaluation with Hyperpolarized 3He Gas”, Radiology, 1999, 210:851–857), asthma (See Altes T. A., Powers P. L., Knight-Scott J., et al., “Hyperpolarized 3He MR Lung Ventilation Imaging in Asthmatics: Preliminary Findings”, J. Magn. Reson. Imaging, 2001, 13:378–384 [herein after “Altes, Powers et al.”]) and cystic fibrosis (See Donnelly L. F., MacFall J. R., McAdams H. P., et al., “Cystic Fibrosis: Combined Hyperpolarized 3He-enhanced and Conventional Proton MR Imaging in the Lung—Preliminary Observations”, Radiology, 1999, 212:885–889). Nonetheless, to fully appreciate many aspects of lung physiology and pathophysiology, an understanding of the gas-flow dynamics during breathing is needed. An approach for obtaining this information is provided in this document.
In the context of lung imaging, some conventional research investigations have made progress toward developing methods for visualizing the time-dependent distribution of gas using hyperpolarized 3He or 129Xe (See Roberts T. P. L., Surkau R., Kauczor H. U., et al., “Helium-3 MRI of Lung Ventilatory Function”, In: Proc. Intl. Soc. Magn. Reson. Med., 5th Meeting, 1997, 307 [herein after “Roberts, Surkau et al.”]; Ruppert K., Brookeman J. R., Mugler III J. P., “Real-time MR Imaging of Pulmonary Gas-Flow Dynamics with Hyperpolarized 3He”, In: Proc. Intl. Soc. Magn. Reson. Med., 6th Meeting, 1998, 1909 [herein after “Ruppert, Brookeman et al.”]; Saam B., Yablonskiy D. A., Gierada D. S., Conradi M. S., “Rapid Imaging of Hyperpolarized Gas Using EPI”, Magn. Reson. Med., 1999, 42:507–514 (herein after “Saam, Yablonskiy et al.”); Chen X. J., Chawla M. S., Hedlund L. W., Möller H. E., MacFall J. R., Johnson G. A., “MR Microscopy of lung Airways with Hyperpolarized 3He”, Magn. Reson. Med., 1998, 39:79–84 [herein after “Chen, Chawla et al.”]; Viallon M., Berthezene Y., Callot V., et al., “Dynamic Imaging of Hyperpolarized 3He Distribution in Rat Lungs Using Interleaved-Spiral Scans”, NMR Biomed, 2000, 13:207–213 [herein after “Viallon, Berthezene et al.”]; Gierada D. S., Saam B., Yablonskiy D., Cooper J. D., Lefiak S. S., Conradi M. S., “Dynamic Echo Planar MR Imaging of Lung Ventilation with Hyperpolarized 3He in Normal Subjects and Patients with Severe Emphysema”, NMR Biomed 2000, 13:176–181; Roberts D. A., Rizi R. R., Lipson D. A., et al., “Detection and Localization of Pulmonary Air Leaks Using Laser-polarized 3He MRI”, Magn. Reson. Med., 2000, 44:379–382; and Schreiber W. G., Markstaller K., Kauczor H. U., et al., “Ultrafast Imaging of Lung Ventilation Using Hyperpolarized Helium-3”, In: Proc. Intl. Soc. Magn. Reson. Med., 7th Meeting, 1999, 129 [herein after “Schreiber, Markstaller et al.”]). However, all of these previous attempts have notable limitations, and none, nor any of their extensions, provide the means to visualize gas-flow dynamics with high spatial resolution, high temporal resolution, and negligible image artifacts.
Rapid conventional gradient-echo pulse sequences lack the desired temporal resolution. Furthermore, since the hyperpolarized magnetization is by nature in a non-equilibrium state, it is beneficial to minimize the number of radio-frequency (RF) pulses needed to create each image. Yet conventional gradient-echo imaging is undesirable in this respect as an RF pulse is required for each line of spatial-frequency-space (k-space) data.
In addition, as is well known from the development of dynamic methods for proton MRI, the rectilinear k-space trajectory used in gradient-echo pulse sequences is sub-optimal for continuous (i.e., “fluoroscopic”) depiction of a dynamic process since only a small number of the raw data lines are located near the center of k space.
For efficient use of the non-equilibrium, hyperpolarized magnetization, gradient-echo-based echo-planar imaging (EPI) is attractive since only one RF pulse per image is required. Saam, Yablonskiy et al. used EPI to acquire axial 1-cm thick dynamic images of the lung with a temporal frame rate of 40 ms and an in-plane spatial resolution of 6–7 mm. Although EPI provides efficient use of the magnetization and high temporal resolution, it is prone to signal loss and/or geometric distortion secondary to the effects of magnetic field inhomogeneities during the relatively long data-sampling period. In addition, the gradient-intensive nature of EPI makes it susceptible to diffusion-induced signal losses when gases are imaged. For example, when applied to lung imaging, attenuation of the MR signal—due to the relatively short T2* (˜10 ms for 3He in the human lung at 1.5 T (See Chen X. J., Möller H. E., Chawla M. S., et al., “Spatially Resolved Measurements of Hyperpolarized Gas Properties in the Lung In vivo. Part II: T2*”, Magn. Reson. Med., 1999, 42:729–737), and due to the high diffusion coefficient (˜2 cm2/s for pure 3He at STP) of the gas—limits the spatial resolution to be greater than approximately 5 mm.
Additionally, slice orientations other than axial demonstrate substantial bulk magnetic susceptibility-induced image distortions due to the structure of the lung, thus reducing the utility of the technique.
Furthermore, the EPI pulse-sequence structure requires an echo time that is on the order of the T2*, resulting in marked signal loss around vessels due to susceptibility effects (See Saam, Yablonskiy, et al.). An interleaved-EPI pulse sequence configuration (See Mugler III J. P., Brookeman J. R., Knight-Scott J., Maier T., de Lange E. E., Bogorad P. L., “Interleaved Echo-Planar Imaging of the Lungs with Hyperpolarized 3He”, In: Proc. Intl. Soc. Magn. Reson. Med., 6th Meeting, 1998, 448) mitigates the susceptibility- and diffusion-induced limitations of EPI. However, an attempt at dynamic hyperpolarized-gas imaging using interleaved-EPI resulted in substantial motion artifacts during periods of rapid gas flow (See Ruppert, Brookeman et al.).
There is therefore a need for an optimal method and system that provides the information required to generate hyperpolarized noble gas images with high spatial and high temporal resolution, and with negligible image artifacts from motion and from field inhomogeneities, such as those caused by magnetic susceptibility interfaces. As no other method for studying the lung can provide both high spatial and high temporal resolution, the present invention provides, among other possibilities, an approach for dynamic imaging of ventilatory function with hyperpolarized gases that shall provide unique and medically relevant information.
Other Applications
Applications such as the measurement of the apparent diffusion coefficient of gas mixtures (See Chen X. J., Moller H. E., Chawla M. S., et al., “Spatially Resolved Measurements of Hyperpolarized Gas Properties in the Lung In vivo. Part I: Diffusion Coefficient,” Magn. Reson. Med., 1999, 42:721–728.), or the determination of the oxygen concentration in gas mixtures (See Deninger A. J., Eberle B., Ebert M., et al., “Quantification of Regional Intrapulmonary Oxygen Partial Pressure Evolution during Apnea by 3He MRI”, J. Magn. Reson., 1999, 141:207–216.), require the acquisition of several images at each spatial location (i.e., slice) of interest. However, the total acquisition time is generally limited, for example by the spin-lattice (T1) relaxation time of the hyperpolarized gas, or, for applications such as human lung imaging, by the subject's ability to suspend respiration. The acquisition time constraint, in turn, limits the number of slices that can be interrogated. Therefore, there is a need in the art for an appropriate high-speed technique that would provide the important benefit of allowing the spatial extent that can be probed per unit time to be substantially increased, as provided by the present invention techniques.
Additionally, there is a need in the art for a high-speed technique for hyperpolarized-gas MRI that permits high temporal resolution to be traded, if desired, for spatial coverage, as also provided by the present invention techniques. Such a technique would also be beneficial for certain other hyperpolarized-gas applications.